Long Term Follow-Up Post Allogeneic HSCT
Endocrine

Updated: October 2010

Thyroid

Subclinical compensated hypothyroidism with elevated TSH and normal serum free T4 occurs in 7-15% of patients in the 1st year following allo-HSCT. Replacement therapy at this point is not mandated but a close follow-up (3 monthly TFT) is warranted. Median time to development of overt hypothyroidism is 4 years in up to 11-15% of patients, particularly in those who have received TBI or head and neck radiation. These patients should be commenced on therapy. Radiation induced and auto-immune thyroiditis can occur.

Radiation to the head and neck results in a dose related increase in malignancy risk. The relative risk of thyroid cancer is increased 3 fold compared to an age and sex matched population. The other factors increasing malignancy risk include female sex, age at HSCT and CGVHD.

Recommendations:

• Yearly TSH, free T4 assessments and management based on results. Referral to endocrinology for abnormal results is advisable.
• High index of suspicion to be maintained to diagnose thyroid malignancy

Gonadal Hormones

Gonadal dysfunction is very common post transplant. The risk of hypogonadism is related to age at transplant (older age associated with greater risk), gender (females >males) and pre-transplant conditioning therapy (TBI, busulfan>single agent melphalan, cyclophosphamide). Men appear to mostly retain normal testosterone levels although infertility is almost universal (recovery seen in 10-15% over several years). In women the risk of hypergonadotrophic hypogonadism is very high and almost universal with TBI or Busulfan conditioning with recovery of ovarian tissue occurring in 5-10% of women years later. The chances of recovery are greater (50%) in patients receiving BEAM chemotherapy. Prepubertal girls have a significantly higher chance of recovery. However if puberty is not achieved by 12-13 years then referral to a specialist is warranted.

Recommendations:

Men:

• Testosterone assessments should be done in men with symptoms of erectile dysfunction or loss of libido. Alternatively it could be routinely assessed at 3 months, 1 year.
• In terms of fertility pre-chemotherapy sperm banking with subsequent assisted fertility techniques should be considered.

Women:

• Women should undergo yearly clinical and endocrinological assessments (FSH, LH, estrogen assays). Patients should be referred to endocrinology for HRT to help maintain libido, sexual function, retain bone density and reduce the risk of cardiovascular and lipid disorders.
• Yearly gynaecological assessments should be done in women with ongoing GVHD as vaginitis, strictures and synechiae formation can be ongoing issues.
• In terms of fertility embryo cryopreservation prior to receipt of chemotherapy is the only technique proven to be beneficial. However, as this requires a delay in treatment of several weeks and a willing partner, it may not be suitable in a number of patients.

Adrenal Gland

Recommendations:

• Chronic steroid use can lead to reversible suppression of pituitary/adrenal axis. Slow terminal tapering of corticosteroids is recommended with formal assessment of adrenal function if patients develop symptoms of adrenal insufficiency on steroid withdrawal. Stress dose steroids should be given in times of acute illness.

• Secondary hyperglycaemia is often seen due to steroid therapy of GVHD and patients should be investigated and managed appropriately, ideally with referral to endocrinology.

The information contained in these guidelines is a statement of consensus of Leukemia/BMT Program of BC professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. Use of these guidelines and documents is at your own risk and is subject to the Leukemia/BMT Program of BC’s terms of use available at Terms of Use.